Abstract LB-358: Plasma HGF level is associated with obesity, increased risk and reduced survival of pancreatic cancer

Abstract

Abstract Background: Obesity is one of the modifiable risk factors for the development and progression of pancreatic cancer. However, the mechanisms of obesity-related pancreatic cancer has not been well defined. In our previous analysis of the genome-wide association data, we identified a significant interaction of obesity with cytokine signaling pathway. Methods: In the current study, we selected several genes from this pathway that code for secreted or membrane proteins and measured the protein levels in plasma samples of 100 pancreatic patients and 100 healthy controls drawn from a case-control study conducted at MD Anderson. Cases and controls were frequency matched by age, sex, race and body mass index (BMI). Plasma levels of HGF (hepatocyte growth factor), MIP-1β (microphage infiltration factor 1-beta), FasL (Fas ligand) and PLA2 (phospholipase A2) were measured using the Luminex and ELISA methods. The protein levels were analyzed in relation to cancer risk and patient survival using analysis of variance, non-parametric test, Kaplan Meier plot, log-rank test, and Cox proportional hazard regression models. Results: A significantly higher level of HGF and MIP-1β and lower level of FasL was observed in cancer patients than in controls, with the mean values of 365.7 vs. 146.2 pg/ml, P< 0.001; 216.5 vs.122.3 pg/ml, P = 0.002, 23.1 versus 29.4 pg/ml, P<0.001, respectively. Individuals with a high HGF or low FasL level had, respectively, 4.6-fold (95% confidence interval [CI] = 2.4-9.1, P<0.001) and 2.9-fold (95% CI = 1.55-5.38, P = 0.001) increased risk of pancreatic cancer with adjustment for other known risk factors. Furthermore, a significant association of HGF level with BMI was observed in cases (R2 = 0.269, P = 0.005). The HGF level (mean ± SE pg/ml) was significantly higher in obese (682±204) than that in overweight (268±40) or normal weight patients (313±71), P = 0.01 and 0.005, respectively. Patients with higher levels of HGF had a significantly reduced overall survival than those with lower levels (9.3 vs. 13.3 months, P = 0.006). Cox proportional hazard regression analysis demonstrated that a higher level of HGF was an independent prognostic factor (Hazard Ratio = 2.61, 95% CI = 1.22-5.64, P = 0.01) after adjusting for BMI, disease stage and other clinical factors. Conclusion: A higher plasma level of HGF was related to obesity and overall survival in pancreatic adenocarcinoma, which may serve as a potential diagnostic and prognostic marker for pancreatic cancer. Citation Format: Dong Yan, Ping Chang, Donghui Li. Plasma HGF level is associated with obesity, increased risk and reduced survival of pancreatic cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-358.